Project Summary/Abstract: Overall Nearly 53 million people (17% of the US population; 18% of children <5 yrs) live within 3 miles of a Superfund remediation site. Superfund sites contain a wide variety of pollutants, including organic chemicals, metals, carbo- naceous material and silica. Although each of these components is capable of damage to organisms, their poten- tial to combine into unique hazardous agents has been understudied. Interestingly, when these agents are pre- sent together, particularly during thermal remediation, they combine to form particulate matter (PM) with chemi- sorbed free radicals that persist in the environment and yet are biologically active. We call these pollutant-particle systems environmentally persistent free radicals (EPFRs). EPFRs are produced during thermal treatment of haz- ardous wastes and nearly 30% of all Superfund sites (excluding groundwater) are remediated by thermal treat- ment. EPFR concentrations near Superfund sites range from 1x1018-4x1019 EPFRs/g (spins/g) of PM. This sug- gests a vast number of US residents are exposed to PM containing EPFRs. LSU Superfund Research Center researchers have shown that these EPFRs 1) induce cardiac and pulmonary dysfunction in the exposed host, 2) are associated with current wheeze in children if present in household dust, and 3) are intermediates in the for- mation of new pollutants such as dioxins. Our Center now seeks to understand how EPFRs induce pulmo- nary/cardiovascular dysfunction and how to attenuate EPFR formation, facilitate EPFR decay, and limit exposure to EPFRs, with the ultimate goal of improving human health and the environment. We will determine how EPFRs are formed, stabilized, and decay and how they catalytically cycle to produce hydroxyl radicals. This will be done using a suite of advanced surface and chemical analyses. Since the airway is a major site of entry of environ- mental PM, we will demonstrate a link between EPFR exposure and poor respiratory health in children using es- tablished community-based birth cohorts. We will explore mechanisms of EPFR-induced asthma and cardiovas- cular disease using mouse models exposed by inhalation. Support cores (Administration, Data Management & Analysis, Community Engagement, Research Experience and Training Coordination, Materials, and Inhalation Toxicology) will provide essential, centralized reagents/services and technological resources allowing for precision of data and economy of effort, and foster interdisciplinary activities. To ensure success, experts in these respective fields were brought together as an External Advisory Committee to advise this Center. The chemistry and physics of EPFRs, let alone their health impacts, are poorly understood, and an interdisciplinary approach is required to address the critical research areas.